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Bivalirudin vs Heparin in NSTEMI and STEMI in Patients on Modern Antiplatelet Therapy in SWEDEHEART (VALIDATE)

Primary Purpose

ST-segment Elevation Myocardial Infarction, Non ST-segment Elevation Myocardial Infarction

Status
Completed
Phase
Phase 4
Locations
Sweden
Study Type
Interventional
Intervention
bivalirudin
Heparin
Sponsored by
Uppsala University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ST-segment Elevation Myocardial Infarction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with a diagnosis of NSTEMI as judged by the physician in accordance with current guideline definitions (positive troponin) or, patients with a diagnosis of STEMI as defined by chest pain suggestive for myocardial ischemia for at least 30 minutes before hospital admission, time from onset of symptoms of less than 24 hours, and an ECG with new ST-segment elevation in two or more contiguous leads of ≥0.2 mV in leads V2-V3 and/or ≥0.1 mV in other leads or a probable new-onset left bundle branch block.
  • PCI of culprit lesion is intended (therapeutic PCI, not primarily diagnostic PCI).
  • Treated with bolus dose of ticagrelor or prasugrel before start of PCI. See 2.6
  • Ability to provide informed consent
  • Age 18 years or older

Exclusion Criteria:

  • Previous randomization in the VALIDATE-SWEDEHEART trial.
  • Known terminal disease with life expectancy less than one year.
  • Patients with known ongoing bleeding
  • Patients with uncontrolled hypertension in the opinion of the investigator
  • Patients with known subacute bacterial endocarditis
  • Patients with known severe renal (GFR < 30 ml/min) and/or liver dysfunction
  • Patients with known thrombocytopenia or thrombocyte function defects
  • Any other contraindication for the study medications.
  • Heparin > 5000U Before arriving to PCI lab or > 3000 U given during angiography before randomization.
  • GpIIb/IIIa inhibitors have been given or are pre-planned to be given during the procedure.

Sites / Locations

  • Lund University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

bivalirudin

heparin

Arm Description

bivalirudin as intravenous bolus of 0,75 mg per kilogram followed by an infusion of 1,75 mg per kilogram per hour

unfractionated Heparin 5 000 IU/ml as intravenous bolus according to local practice

Outcomes

Primary Outcome Measures

Death, Myocardial infarction and major bleeding event

Secondary Outcome Measures

Death, Myocardial infarction and major bleeding events in the subgroups NSTEMI and STEMI
Time to primary endpoints (death, myocardial infarction and major bleeding event)
Time to individual components of the primary end point (death, myocardial infarction and major bleeding).
Number of events where primary endpoints (death, myocardial infarction and major bleeding event) and stroke have been registered
The primary end point combined with stroke as reported in the Swedish national patient registry.
Number of events where primary endpoints (death, myocardial infarction and major bleeding event) have been registered in heparin subgroups (U/kg, groups with certain max ACT values etc)
TIMI flow grade after PCI
Time to re-hospitalization with reinfarction
Time to re-hospitalization with reinfarction as reported in Swedeheart
Time to all-cause death or re-hospitalization with myocardial infarction
Time to target vessel revascularization
Time to target vessel revascularization as reported in SWEDEHEART.
Time to target lesion revascularization
Time to target lesion revascularization as reported in SWEDEHEART
Time to stent thrombosis
Time to stent thrombosis as reported in SWEDEHEART.
Time to restenosis
Time to restenosis as reported in SWEDEHEART.
Time to re-hospitalization with heart failure
Time to re-hospitalization with heart failure as reported in SWEDEHEART.
Heart failure and complications of PCI during index hospitalization
Heart failure and complications of PCI during index hospitalization as reported in SWEDEHEART
Minor bleeding during index hospitalization
Minor bleeding during index hospitalization as reported in SWEDEHEART
Length of index hospital stay
Length of index hospital stay as reported in SWEDEHEART
Bail-out use of GpIIb/IIIa
Bail-out use of GpIIb/IIIa inhibitors during PCI

Full Information

First Posted
November 27, 2014
Last Updated
May 18, 2017
Sponsor
Uppsala University
Collaborators
Lund University
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1. Study Identification

Unique Protocol Identification Number
NCT02311231
Brief Title
Bivalirudin vs Heparin in NSTEMI and STEMI in Patients on Modern Antiplatelet Therapy in SWEDEHEART
Acronym
VALIDATE
Official Title
Bivalirudin vs Heparin in NSTEMI and STEMI in Patients on Modern Antiplatelet Therapy in SWEDEHEART A Multicenter, Prospective, Randomized Controlled Clinical Trial Based on the SWEDEHEART Platform
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
June 2014 (undefined)
Primary Completion Date
March 2017 (Actual)
Study Completion Date
March 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Uppsala University
Collaborators
Lund University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this trial we test the hypothesis that PCI and bivalirudin is superior to heparin alone (according to local protocol) in reducing death, MI, and major bleeding in patients with NSTEMI or STEMI at 180 days (primary end point), treated with ticagrelor or prasugrel.
Detailed Description
The follow up of endpoints will be performed using SWEDEHEART and national registries. Follow up of primary endpoints and stroke will also be performed by telephone contacts with the patients or first degree relatives by a nurse phone call after 7 days and 180 days. The nurses will also accumulate hospital record information on these endpoints. A central adjudication will be performed for all reported primary endpoints for the first 180 days follow up. Every site will prepare source documents for the event and send it to UCR for central adjudication by an independent committee.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ST-segment Elevation Myocardial Infarction, Non ST-segment Elevation Myocardial Infarction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6012 (Actual)

8. Arms, Groups, and Interventions

Arm Title
bivalirudin
Arm Type
Experimental
Arm Description
bivalirudin as intravenous bolus of 0,75 mg per kilogram followed by an infusion of 1,75 mg per kilogram per hour
Arm Title
heparin
Arm Type
Active Comparator
Arm Description
unfractionated Heparin 5 000 IU/ml as intravenous bolus according to local practice
Intervention Type
Drug
Intervention Name(s)
bivalirudin
Other Intervention Name(s)
Angiox
Intervention Description
Will be administered as an intravenous bolus of 0.75 mg per kilogram, followed by an infusion of 1.75 mg per kilogram per hour). Bivalirudin will be administered alone or with a low dose of heparin up to 3000U heparin in lab or up to 5000 U given pre-hospital according to local practice.
Intervention Type
Drug
Intervention Name(s)
Heparin
Other Intervention Name(s)
Heparin 5000 IU/ml i.v. ,Leo Pharma
Intervention Description
Treatment with unfractionated Heparin 5000 IU/ml i.v. ,Leo Pharma, Sweden, (the control group). Heparin in the control group is administered as an intravenous or intra-arterial bolus according to local practice. A dose of 70-100 U/kg is recommended
Primary Outcome Measure Information:
Title
Death, Myocardial infarction and major bleeding event
Time Frame
180 days
Secondary Outcome Measure Information:
Title
Death, Myocardial infarction and major bleeding events in the subgroups NSTEMI and STEMI
Time Frame
180 days
Title
Time to primary endpoints (death, myocardial infarction and major bleeding event)
Description
Time to individual components of the primary end point (death, myocardial infarction and major bleeding).
Time Frame
180 days
Title
Number of events where primary endpoints (death, myocardial infarction and major bleeding event) and stroke have been registered
Description
The primary end point combined with stroke as reported in the Swedish national patient registry.
Time Frame
180 days
Title
Number of events where primary endpoints (death, myocardial infarction and major bleeding event) have been registered in heparin subgroups (U/kg, groups with certain max ACT values etc)
Time Frame
180 days
Title
TIMI flow grade after PCI
Time Frame
180 days
Title
Time to re-hospitalization with reinfarction
Description
Time to re-hospitalization with reinfarction as reported in Swedeheart
Time Frame
180 days
Title
Time to all-cause death or re-hospitalization with myocardial infarction
Time Frame
180 days
Title
Time to target vessel revascularization
Description
Time to target vessel revascularization as reported in SWEDEHEART.
Time Frame
180 days
Title
Time to target lesion revascularization
Description
Time to target lesion revascularization as reported in SWEDEHEART
Time Frame
180 days
Title
Time to stent thrombosis
Description
Time to stent thrombosis as reported in SWEDEHEART.
Time Frame
180 days
Title
Time to restenosis
Description
Time to restenosis as reported in SWEDEHEART.
Time Frame
180 days
Title
Time to re-hospitalization with heart failure
Description
Time to re-hospitalization with heart failure as reported in SWEDEHEART.
Time Frame
180 days
Title
Heart failure and complications of PCI during index hospitalization
Description
Heart failure and complications of PCI during index hospitalization as reported in SWEDEHEART
Time Frame
180 days
Title
Minor bleeding during index hospitalization
Description
Minor bleeding during index hospitalization as reported in SWEDEHEART
Time Frame
180 days
Title
Length of index hospital stay
Description
Length of index hospital stay as reported in SWEDEHEART
Time Frame
180 days
Title
Bail-out use of GpIIb/IIIa
Description
Bail-out use of GpIIb/IIIa inhibitors during PCI
Time Frame
180 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with a diagnosis of NSTEMI as judged by the physician in accordance with current guideline definitions (positive troponin) or, patients with a diagnosis of STEMI as defined by chest pain suggestive for myocardial ischemia for at least 30 minutes before hospital admission, time from onset of symptoms of less than 24 hours, and an ECG with new ST-segment elevation in two or more contiguous leads of ≥0.2 mV in leads V2-V3 and/or ≥0.1 mV in other leads or a probable new-onset left bundle branch block. PCI of culprit lesion is intended (therapeutic PCI, not primarily diagnostic PCI). Treated with bolus dose of ticagrelor or prasugrel before start of PCI. See 2.6 Ability to provide informed consent Age 18 years or older Exclusion Criteria: Previous randomization in the VALIDATE-SWEDEHEART trial. Known terminal disease with life expectancy less than one year. Patients with known ongoing bleeding Patients with uncontrolled hypertension in the opinion of the investigator Patients with known subacute bacterial endocarditis Patients with known severe renal (GFR < 30 ml/min) and/or liver dysfunction Patients with known thrombocytopenia or thrombocyte function defects Any other contraindication for the study medications. Heparin > 5000U Before arriving to PCI lab or > 3000 U given during angiography before randomization. GpIIb/IIIa inhibitors have been given or are pre-planned to be given during the procedure.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Erlinge
Organizational Affiliation
Lund University, Lund, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lund University
City
Lund
ZIP/Postal Code
221 85
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
34903034
Citation
James S, Koul S, Andersson J, Angeras O, Bhiladvala P, Calais F, Danielewicz M, Frobert O, Grimfjard P, Gotberg M, Henareh L, Ioanes D, Jensen J, Linder R, Lindroos P, Omerovic E, Panayi G, Ramunddal T, Sarno G, Ulvenstam A, Voltz S, Wagner H, Wikstrom H, Ostlund O, Erlinge D. Bivalirudin Versus Heparin Monotherapy in ST-Segment-Elevation Myocardial Infarction. Circ Cardiovasc Interv. 2021 Dec;14(12):e008969. doi: 10.1161/CIRCINTERVENTIONS.120.008969. Epub 2021 Dec 14.
Results Reference
derived
PubMed Identifier
34514849
Citation
Bergman S, Mohammad MA, James SK, Angeras O, Wagner H, Jensen J, Schersten F, Frobert O, Koul S, Erlinge D. Clinical Impact of Intraprocedural Stent Thrombosis During Percutaneous Coronary Intervention in Patients Treated With Potent P2Y12 inhibitors - a VALIDATE-SWEDEHEART Substudy. J Am Heart Assoc. 2021 Sep 21;10(18):e022984. doi: 10.1161/JAHA.121.022984. Epub 2021 Sep 13. Erratum In: J Am Heart Assoc. 2022 Aug 16;11(16):e020782.
Results Reference
derived
PubMed Identifier
34011198
Citation
Rylance RT, Wagner P, Omerovic E, Held C, James S, Koul S, Erlinge D. Assessing the external validity of the VALIDATE-SWEDEHEART trial. Clin Trials. 2021 Aug;18(4):427-435. doi: 10.1177/17407745211012438. Epub 2021 May 20.
Results Reference
derived
PubMed Identifier
33589539
Citation
Jamaly S, Redfors B, Omerovic E, Carlsson L, Karason K. Prognostic significance of BMI after PCI treatment in ST-elevation myocardial infarction: a cohort study from the Swedish Coronary Angiography and Angioplasty Registry. Open Heart. 2021 Feb;8(1):e001479. doi: 10.1136/openhrt-2020-001479.
Results Reference
derived
PubMed Identifier
32143733
Citation
Olsson A, Ring C, Josefsson J, Eriksson A, Rylance R, Frobert O, James S, Sparv D, Erlinge D. Patient experience of the informed consent process during acute myocardial infarction: a sub-study of the VALIDATE-SWEDEHEART trial. Trials. 2020 Mar 6;21(1):246. doi: 10.1186/s13063-020-4147-0.
Results Reference
derived
PubMed Identifier
31387441
Citation
Wester A, Attar R, Mohammad MA, Andell P, Hofmann R, Jensen J, Szummer K, Erlinge D, Koul S. Impact of Baseline Anemia in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: A Prespecified Analysis From the VALIDATE-SWEDEHEART Trial. J Am Heart Assoc. 2019 Aug 20;8(16):e012741. doi: 10.1161/JAHA.119.012741. Epub 2019 Aug 7.
Results Reference
derived
PubMed Identifier
28844201
Citation
Erlinge D, Omerovic E, Frobert O, Linder R, Danielewicz M, Hamid M, Swahn E, Henareh L, Wagner H, Hardhammar P, Sjogren I, Stewart J, Grimfjard P, Jensen J, Aasa M, Robertsson L, Lindroos P, Haupt J, Wikstrom H, Ulvenstam A, Bhiladvala P, Lindvall B, Lundin A, Todt T, Ioanes D, Ramunddal T, Kellerth T, Zagozdzon L, Gotberg M, Andersson J, Angeras O, Ostlund O, Lagerqvist B, Held C, Wallentin L, Schersten F, Eriksson P, Koul S, James S. Bivalirudin versus Heparin Monotherapy in Myocardial Infarction. N Engl J Med. 2017 Sep 21;377(12):1132-1142. doi: 10.1056/NEJMoa1706443. Epub 2017 Aug 27.
Results Reference
derived

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Bivalirudin vs Heparin in NSTEMI and STEMI in Patients on Modern Antiplatelet Therapy in SWEDEHEART

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